Astex Pharmaceuticals Announces Publication of Key Clinical Data for Guadecitabine (SGI-110) in The Lancet Oncology

Astex Pharmaceuticals Announces Publication of Key Clinical Data for Guadecitabine (SGI-110) in The Lancet Oncology

  • Guadecitabine (SGI-110) is a novel, next-generation hypomethylating agent (HMA) which reverses aberrant DNA methylation by inhibiting DNA methyltransferase enzymes.
  • This publication describes a first-in-human pharmacokinetic and pharmacodynamic guided dose-escalation study of guadecitabine (SGI-110) in adults with myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), refractory to, or relapsed after, standard treatment.

Pleasanton, CA, USA, August 18, 2015. Astex Pharmaceuticals, a pharmaceutical company dedicated to the discovery and development of novel small molecule therapeutics, announces the publication of key clinical data for the novel hypomethylating agent (HMA) guadecitabine (SGI-110) in the prestigious journal, The Lancet Oncology. The publication, entitled “Pharmacokinetic and Pharmacodynamic-guided Phase 1 study of the novel hypomethylating drug guadecitabine (SGI-110) in myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML)”, was released online on August 18, 2015 at http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00038-8/abstract.

The publication describes the first-in-human clinical trial of 93 heavily pre-treated patients (74 AML and 19 MDS) treated with guadecitabine and reports that the drug is welltolerated, easily administered, and biologically and clinically active in both MDS and AML patients who relapsed after standard of care. Importantly, potent dose-related DNA demethylation is associated with clinical responses in patients treated with guadecitabine, with responders showing significantly more demethylation than non-responders. The study was conducted at 13 leading cancer centers in the US and Canada.

The results described in this publication were used to inform the design of a large Phase 2 study in both treatment naïve and relapsed / refractory AML and MDS, in which over 300 patients were treated with guadecitabine, and a recently-commenced 800-patient global Phase 3 study (ASTRAL-1), in which guadecitabine is being compared with physician’s choice of decitabine, azacitidine, or low-dose cytarabine in treatment naïve AML patients unfit to receive, or unsuitable for, intensive induction chemotherapy.

Lead Author, Jean-Pierre Issa, MD of Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine said “This study demonstrates that guadecitabine is safe, and showed that the drug resulted in improved PK exposure and PD demethylation over what has been reported for the first-generation HMAs. It also confirmed the importance of DNA demethylation as a PD marker for clinical response”. Dr. Issa added “Guadecitabine’s improved PK and PD profile may improve clinical outcomes in patients with hematologic malignancies, and may also make the drug useful in the treatment of solid tumors, an area in which first generation HMAs are not currently approved .”

Hagop Kantarjian, MD, of The University of Texas MD Anderson Cancer Center, the senior author of the study said: “In this study we observed induced clinical responses in heavily pre-treated patients including prior treatment with current HMAs. Together with the results of a large Phase 2 study to be published later, these data support further investigation, including the recently commenced global Phase 3 study in treatment-naïve AML patients”.

About guadecitabine (SGI-110): Guadecitabine is a novel next-generation small molecule, DNA hypomethylating agent designed to be administered as a single, small volume, subcutaneous injection. Guadecitabine demonstrated activity in restoring silenced tumor suppressor gene expression in cancer cells by reversal of DNA methylation and inducing responses in previously treated MDS and AML patients. Guadecitabine is wholly owned by Astex Pharmaceuticals.

About the SGI-110 study in MDS and AML patients (Study SGI-110-01): The SGI-110-01 trial is a large (over 400 patients) randomized Phase 1/2 study in patients with MDS or AML. The trial included a Phase I does escalation stage (93 patients) and a randomized Phase 2 stage (308 patients) that investigated four patient populations: treatment naïve and relapsed / refractory AML and MDS, and also explored both a dailyx5 and a dailyx10 regimen. Additional information about the study can be found online at http://clinicaltrials.gov/ct2/show/NCT01261312.

About the ASTRAL-1 SGI-110 study (Study SGI-110-04) ASTRAL-1 is a large, global, randomized 800-patient study of guadecitabine (SGI-110) in treatment naïve AML patients who are unfit to receive, or unsuitable for, intensive induction chemotherapy. The trial commenced in March 2015, and compares guadecitabine with physician’s choice of low-dose cytarabine, decitabine or azacitidine. Additional information about the study can be found online at https://www.clinicaltrials.gov/ct2/show/NCT02348489.

About Astex Pharmaceuticals

Astex Pharmaceuticals is dedicated to the discovery and development of novel small molecule therapeutics with a focus on oncology. Astex is developing a proprietary pipeline of novel therapies and has a number of partnered products being developed under collaborations with leading pharmaceutical companies. In October 2013, Astex was acquired by Otsuka Pharmaceutical Co. Ltd., Tokyo, Japan, and operates as a wholly owned subsidiary. The Otsuka Group employs approximately 43,000 people globally, and its products are available in more than 80 countries worldwide.

For more information about Astex Pharmaceuticals, please visit http://www.astx.com

For more information about Otsuka Pharmaceutical, please visit http://www.otsuka.com/en/

CONTACT:
Martin Buckland
Chief Corporate Officer
Astex Pharmaceuticals, Inc.
4420 Rosewood Drive, Suite 200
Pleasanton, CA 94588
Tel: +1 (925) 560-0100
Email: email_mb

Astex Pharmaceuticals Presents Final Results of Phase 2 Study of SGI-110 in Treatment Naive Elderly Acute Myeloid Leukaemia at the European Hematology Association Meeting

Astex Pharmaceuticals Presents Final Results of Phase 2 Study of SGI-110 in Treatment Naïve Elderly Acute Myeloid Leukemia at the European Hematology Association Meeting

Dublin, CA, USA and Cambridge, UK, June 16, 2014 – Astex Pharmaceuticals, a pharmaceutical company dedicated to the discovery and development of novel small molecule therapeutics, presented the final results of a Phase 2 study of SGI-110, a novel hypomethylating agent in elderly Acute Myeloid Leukemia (AML) in an oral session on June 14 at the European Hematology Association meeting held in Milan, Italy (June 12-15).

The results focused on clinical responses as well as safety of 2 doses of SGI-110 (60 and 90 mg/m2 /d) given as a subcutaneous injection daily x5 every 28 days in treatment naïve elderly AML patients not suitable for intensive chemotherapy enrolled in study SGI-110-01.

The study enrolled and treated 51 patients. The primary endpoint of Overall Complete Remission (CR or CR with incomplete normal count recovery (CRi)) was achieved in 28 of 51 patients (55%). The CR rate was achieved in 17 of 51 patients (33%). There were no major differences between the clinical responses and safety of the two doses of SGI-110. The most common Grade ≥ 3 Adverse Events were the expected and reversible myelosuppression adverse events: febrile neutropenia, thrombocytopenia, and anemia. All patients achieved potent DNA demethylation, and patients with CR or CRi had better Overall Survival than non-responders.

“We are pleased with the promising clinical activity and safety profile of SGI-110 as a next generation hypomethylating agent” said Mohammad Azab, MD, President and Chief Medical Officer of Astex Pharmaceuticals, Dublin, CA, USA. “These results support the Phase 3 development of SGI-110 in treatment naive elderly AML not suitable for intensive chemotherapy.”

About SGI-110:

SGI-110 is a novel small molecule, DNA-hypomethylating agent administered as a single small volume subcutaneous injection. SGI-110 demonstrated activity in restoring silenced tumor suppressor gene expression in cancer cells by reversal of DNA methylation and inducing responses in previously treated MDS and AML patients. SGI-110 is wholly owned by Astex Pharmaceuticals.

About the SGI-110 study in MDS and AML patients (Study SGI-110-01):

The SGI-110-01 trial is a randomized Phase 1/2 study in patients with Myelodysplastic Syndromes (MDS) and AML. The trial completed its Phase 1 dose escalation segment showing extended half-life and prolonged exposure window to the active ingredient decitabine compared to decitabine IV as well as potent DNA demethylation and multiple clinical responses in heavily pretreated MDS and AML patients.

This study is currently in a Phase 2 dose expansion segment with several cohorts including refractory/relapsed AML and treatment naïve elderly AML ineligible for intensive chemotherapy treated with dailyx5 and dailyx10 regimens. Additional information about the study can be found online at http://clinicaltrials.gov/ct2/show/NCT01261312.

About Astex Pharmaceuticals Astex Pharmaceuticals is dedicated to the discovery and development of novel small molecule therapeutics with a focus on oncology. Astex is developing a proprietary pipeline of novel therapies and has a number of partnered products being developed under collaborations with leading pharmaceutical companies. Astex is a subsidiary of Otsuka America, Inc. (OAI), a holding company established in the U.S. in 1989. OAI is wholly owned by Otsuka Pharmaceutical Co., Ltd. The Otsuka Group employs approximately 42,000 people globally, and its products are available in more than 80 countries worldwide. Otsuka welcomes you to visit its global website at https://www.otsuka.co.jp/en.

For more information about Astex Pharmaceuticals, please visit http://www.astx.com.

CONTACT:

Jeremy Carmichael
Senior Director of Business Development Astex Pharmaceuticals
436 Cambridge Science Park
Milton Road
Cambridge CB4 0QA
United Kingdom
Tel: +44 (0) 1223 226200
Email: email_jc

Peggy Bickerton
Corporate Communications Astex Pharmaceuticals
4140 Dublin Blvd.
Suite 200
Dublin,CA 94568
USA Tel: +1 (925) 560-2803
Email: email_pb

Astex Earns Milestone Payment on Initiation of Phase 3 Study

Astex Earns Milestone Payment on Initiation of Phase 3 Study

Cambridge, UK, and Dublin, CA, USA, 4th March 2014, Astex Pharmaceuticals, a pharmaceutical company dedicated to the discovery and development of novel small molecule therapeutics, announced  hat it has received a milestone payment triggered by the commencement, by Novartis, of a Phase 3 study of LEE011, a small-molecule inhibitor of cyclin-dependent kinases (CDK) 4 and 6. LEE011 was discovered as part of a drug discovery collaboration between Astex and Novartis announced in December 2005.

LEE011 specifically and selectively inhibits CDK4 and CDK6 leading to cell cycle arrest in the G1 phase, and suppressing DNA synthesis may inhibit cancer cell growth. LEE011, in combination with other agents, has shown promising activity in pre-clinical studies in melanoma and breast cancer. The current Phase 3 study is designed to evaluate the efficacy and safety of LEE011 in combination with letrozole in ER+ve, HER2ve postmenopausal woman with advanced breast cancer1.

1 Study of Efficacy and Safety of LEE011 in Postmenopausal Women With Advanced Breast Cancer. ClinicalTrials.gov Identifier: NCT01958021.

About Astex Pharmaceuticals

Astex Pharmaceuticals is dedicated to the discovery and development of novel small molecule therapeutics with a focus on oncology. Astex is developing a proprietary pipeline of novel therapies and has a number of partnered products being developed under collaborations with leading pharmaceutical companies. In October 2013, Astex was acquired by Otsuka Pharmaceutical Co. Ltd., Tokyo, Japan and operates as a wholly owned subsidiary.

For more information about Astex Pharmaceuticals, please visit http://www.astx.com

CONTACT:
Jeremy Carmichael
Senior Director of Business Development
Astex Pharmaceuticals
436 Cambridge Science Park
Milton Road
Cambridge CB4 0QA
United Kingdom
Tel: +44 (0) 1223 226200
Email: email_jc